comparison of paclitaxel/carboplatin and lonafarnib to paclitaxel/carboplatin for first-line treatment of ovarian cancer

Conditions: Epithelial Ovarian Cancer

Summary: the purpose of this study is to compare the effects of paclitaxel/carboplatin and lonafarnib to those of paclitaxel/carboplatin in primary treatment of patients with epithelial ovarian cancer.

today the standard therapy for patients with advanced ovarian carcinoma is paclitaxel and carboplatin. lonafarnib is a farnesyl transferase inhibitor (fti) that is active against a broad spectrum of tumor cell lines in vitro and tumor xenografts in nude mice. lonafarnib has single-agent antitumor activity as well as enhanced activity in combination with taxanes in a number of tumor cell lines and in vivo models.

Eligibility criteria:
inclusion criteria: * previously untreated patients with a histologically confirmed diagnosis of cancer of the ovary, the fallopian tube or extra-ovarian papillary serous tumors figo stage iib-iv, regardless of measurable or non-measurable disease * age \>= 18 years * ecog performance status \<= 2 * life-expectancy of at least 6 months * adequate bone marrow, renal and hepatic function: wbc \>= 3.0 x 10\^9/l; neutrophils (anc) \>= 1.5 x 10\^9/l; platelets \>= 100 x 10\^9/l; hemoglobin \> 6 mmol/l (\> 10.0 g/dl); bilirubin \ = 50 ml/min according to jelliffe or cockroft-gault formula * patients who have given their signed and written informed consent to participate in the trial after fully understanding the implication and constraints of the protocol * patients must be geographically accessible for treatment and follow-up * time between definitive surgery and randomization into the study \<= 6 weeks exclusion criteria: * ovarian tumors of low malignant potential (borderline tumors) * non-epithelial ovarian or mixed epithelial/nonepithelial tumors (e.g. mixed mullerian tumors) * patients who have received previous chemotherapy or radiotherapy * prior treatment with ft inhibitors * patients with a prior diagnosis of any malignancy not cured by surgery alone less than 5 years before study entry (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) * complete bowel obstruction or the presence of symptomatic brain metastases * concurrent severe medical problems unrelated to malignancy which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy * patients with a history of seizure disorder or central nervous system disorders; pre-existing motor or sensory neurologic pathology or symptoms \> nci grade 1 * history of congestive heart failure (nyha classification \> 2, even if medically controlled. * history of clinical and electrocardiographically documented myocardial infarction within the last 6 months. * history of atrial or ventricular arrhythmias (\>= lown ii) * patients with significant fridericia qtc (qtcf) prolongation at baseline (ie. qtcf \>= 470 msec) * patients with severe active infection * patients with a history of severe hypersensitivity reactions to products containing cremophor el (cyclosporin or vitamin k) and/or patients with known hypersensitivity to compounds chemically related to carboplatin and paclitaxel * women with childbearing potential and who are sexually active and unwilling to use a medically acceptable method of contraception (oral contraceptive, diaphragm with spermicide, intrauterine device, condom with spermicide) * women who are pregnant or breast feeding * administration of other anticancer therapy or simultaneous chemotherapeutic and/or hormonal drugs, or radiotherapy during the study treatment period (except: hormonal replacement therapy and/or steroid antiemetics) * patients who are participating in any other clinical study * dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent